HIDRADENITIS

 

SUPPURATIVA

 

Epidemiology

 

Hidradenitis (HS) has a point prevalence of up to 4.1 percent based on objective findings, and a 1-year prevalence of 1 percent based on patient recall. This prevalence was refuted by another group of investigators, who determined a prevalence of only 1/3000. It is more common in females, with reported female-male ratios ranging from 2:1 to 5:1. The reason for female preponderance is unknown. HS rarely develops before puberty or after menopause, although persistence into menopause is not uncommon. The average age of onset is 23 years. Although the disease may develop in any apocrine gland-bearing skin, genitofemoral lesions are more prevalent in women, whereas axillary involvement does not demonstrate a gender predilection.

Etiology and Pathogenesis

Little is known about the pathogenic basis of HS. Unfortunately, only a few limited studies have attempted to clarify etiology.

 

ADNEXAL STRUCTURES

 

Classically, HS was thought to represent a primary disorder of apocrine glands, and was also referred to as apocrinitis.⁵⁶ The anatomic location of disease in apocrine-bearing skin supported this concept. Shelley and Cahn provided additional support of this concept by hypothesizing that poral occlusion of the apocrine duct reproduced the clinical and pathologic lesions using their experimental model.⁶⁵

 

HIDRADENITIS SUPPURATIVA AT

AGLANCE

• Common disorder with a point-prevalence of 4.1 percent and female preponderance.
• A chronic and recurrent disorder, usually developing at puberty and most commonly involving the genitofemoral area or axillae.
• Primary pathogenic event is believed to be follicular occlusion with subsequent inflammation, secondary adnexal gland involvement, fibrosis, and scarring.
• Pathologic features may include follicular hyperkeratosis, folliculitis, abscess formation, sinus tract formation, fibrosis, and granuloma formation.
• Surgery may sometimes be curative; antibiotics, retinoids, hormonal treatments, and some immunosuppressive medications may benefit some patients.

More recent publications have refuted the concept that this primary event in HS is apocrine gland inflammation and postulate that apocrine glands become secondarily affected. HS is now generally considered to be a disorder of the follicular epithelium, with follicular occlusion giving rise to clinical findings. Follicular hyperkeratosis is the initial event, leading to occlusion, occasional secondary apocrine involvement, and follicular rupture with resultant inflammation and possibly secondary infection. Pathologic studies have supported this concept by demonstrating follicular obstruction, the absence of apocrine glands, and minimal or absent apocrine gland inflammation in specimens of HS.

The concept of the follicular occlusion tetrad stems from the concept that HS, acne vulgaris, pilonidal sinus, and dissecting cellulitis all share follicular occlusion as an inciting event that eventually leads to disease expression.

 

GENETIC FACTORS

 

A family history of HS may be elicited in 26 percent of patients. Several studies have not demonstrated HLA associations. Others studies have suggested an autosomal dominant mode of inheritance with single gene transmission. No genetic locus has been identified.

 

ASSOCIATED DISEASE

 

The co-existence of HS and Crohn disease, particularly with perianal involvement, has been associated with a more fulminant course. Perianal Crohn disease may be clinically indistinguishable from perianal HS. Other reported associations include pyoderma gangrenosum, nephrotic syndrome, and amyloidosis, Dowling-Degos disease, and arthropathy.

 

HORMONES AND ANDROGENS

 

The tendency of HS to develop at puberty or postpubertally suggests an androgen influence. Additionally, disease flares have been reported postpartum, in association with the oral contraception pill, and in the premenstrual period (approximately 50 percent of patients). Antiandrogen therapy has also demonstrated therapeutic benefit in some studies.^87-90 However, no biochemical evidence of hyperandrogenism was found in 66 women with HS. Additionally, unlike the sebaceous glands, the apocrine glands are not affected by androgens. Thus, the influence of androgens on HS is unclear.

 

OBESITY

 

Obesity is unlikely to be a causal factor in HS but is often regarded as an exacerbating factor by increasing shearing forces, occlusion, keratinocyte hydration, and maceration. Obesity may also exacerbate disease by creating a state of androgen excess. Weight reduction is recommended for overweight patients and may help to control disease.

 

BACTERIAL INFECTION

 

The role of bacterial infection in HS is unclear. It is believed that the pathogenic role is similar to the role of bacteria in acne. Antibacterial agents are commonly used as therapy. Bacterial involvement is thought by some authors to occur secondarily. Routine cultures are often negative, but numerous bacteria have been recovered from lesions. Staphylococcus aureus and coagulase-negative staphylococci are most frequently isolated. However, other bacteria, including streptococci, gram-negative rods, and anaerobes, have also been identified. These are likely to be colonizing bacteria rather than causative bacteria.

 

SMOKING

 

The use of tobacco products is more common in HS patients than in healthy controls. One study determined that 70 percent of their 43 patient cohort with perineal HS were smokers. It is postulated that smoking affects polymorphonuclear cell chemotaxis.⁶¹ Smoking cessation may improve the clinical course of diseases.

Box 83-4 Differential Diagnosis of Hidradenitis Suppurativa

• Abscesses (including from methicillin-resistant Staphylococcus aureus)
• Furuncles/carbuncles
• Actinomycosis
• Cat scratch disease
• Donovanosis
• Lymphogranuloma venereum
• Lymphadenitis
• Infected Bartholin cyst
• Crohn disease
• Ulcerative colitis
• Tuberculosis
• Tularemia
• Ruptured epidermal cyst

From Jovanovic M et al: Hidradenitis suppurativa, in emedicine, edited by Siegel D et al. (http://www.emedicine.com), 2006.

Clinical Findings

HS is a chronic disease with a variable clinical course. The diagnosis of HS is clinical, and a biopsy is rarely needed (Box 83-4). Clinical diagnostic criteria are wide and include recurrent disease, scarring, and multifocal location.

HS involves apocrine-bearing skin with a predilection for intertriginous areas. The sites affected in order of decreasing frequency include: axillary, inguinal, perineal and perianal, mammary and inframammary, buttocks, pubic region, chest, scalp, retroauricular, and eyelid.

Three stages of disease are recognized. In the primary stage, abscesses develop in isolated locations. The secondary stage involves the development of sinus tracts with scars bridging individual lesions. The tertiary stage shows coalescing lesions with scarring and sinus tracts, inflammation, and chronic discharge.

The disease onset is insidious and shows variable severity. Otherwise healthy postpubertal individuals initially may experience slight discomfort or pruritus. After this, a tender papule or deep-seeded nodule (0.5 to 2.0 cm) ensues . Pustules may also be visualized . This nodule may slowly resolve or may expand and coalesce with surrounding nodules to form large painful inflammatory abscesses. These abscesses are rounded without central necrosis and may resolve or rupture spontaneously, producing a purulent discharge . Eventual healing may result in scarring with fibrosis

, dermal contractures and rope-like elevation of the skin , and double-ended comedones . Sinus tracts may also develop . Sinuses have been reported to involve deep tissue, including muscle and fascia, urethra, and bowel. The process then recurs in an adjacent area or different apocrine-bearing site.

 

LABORATORY TESTS

 

Patients with acute lesions of HS may demonstrate an increase in the erythrocyte sedimentation rate or C-reactive protein. If there is any concern over infection, then deep cultures (not skin surface) from lesions should be conducted and submitted for bacterial, tuberculosis, and fungal cultures.

 

SPECIAL TESTS

 

Ultrasonography of the follicles and dermis may reveal abscess formation and abnormalities in the deep part of the follicle, but is rarely indicated. Recently, magnetic resonance imaging features of the skin and subcutaneous tissue have been described. Such features included marked thickening of the skin, induration of the subcutaneous tissues, and multiple subcutaneous abscesses.

 

Pathology

 

The early lesions of HS demonstrate follicular hyperkeratosis. Other dermal features include active folliculitis or abscess, sinus tract formation, fibrosis, and granuloma formation. There is evidence of an inverse relationship between fibrosis and inflammation, supporting the concept that fibrosis corresponds to areas of chronic involvement.⁶⁸ Histologic feature examination of adnexal structures reveals inflammation of the apocrine glands in only one-third of cases. Interestingly, involvement of eccrine glands (25 percent) has been reported to be more common than apocrine glands (12 percent).Poral occlusion or cyst formation may be noted. The subcutis may demonstrate some fibrosis, fat necrosis, or inflammation.

Complications

 

QUALITY OF LIFE

 

Patients with HS experience a significant degree of morbidity when quality of life is measured by the Dermatology Life Quality Index. The highest scores relate to disease-associated pain. Quality of life measurements are lower than other dermatologic diseases that have been investigated using this tool.¹⁰⁵ Loss of workdays is a socioeconomic consequence. Women lose significantly more days of work (mean, 2.9 days) than men (mean, 1.7 days).

 

SYSTEMIC COMPLICATIONS

 

Local infection may develop and lead to septicemia. A case of lumbosacral epidural abscess has been reported. Anemia or leukocytosis may be detected, but does not tend to be significant clinically.

 

LOCAL COMPLICATIONS

 

Scarring may limit mobility. Anal, urethral, or rectal strictures may develop from chronic genitofemoral inflammation. Urethral fistulas have also been reported. Additionally, disfiguring persistent penile, scrotal, or vulvar lymphedema may develop, giving rise to significant functional impairment. This lymphedema is thought to result from fibrosis and resultant lymphatic channel obstruction. Surgical reconstruction may be necessary. Squamous cell carcinoma (SCC) may rarely develop in chronically inflamed and scarred areas in individuals with long-standing disease. SCC has been reported in 3.2 percent of patients with perianal HS lasting 20 to 30 years. SCC is most common in men in the anogenital region. These carcinomas tend to be more aggressive locally and are associated with a higher incidence of metastatic disease and mortality. One case of paraneoplastic neuropathy has been described in association with SCC complicating severe perineal HS. Clinicians should have a low threshold for biopsying any non-healing lesion localizing to an area of chronic HS. One case-controlled Swedish study found that the overall incidence of malignancy, including non-melanoma skin cancer, is increased in patients with HS.

 

Treatment

 

The objective of patient management is prevention of the development of primary lesions as well as resolution, amelioration, or regression of secondary disease features such as scarring or sinus tract formation. The literature reveals only three randomized controlled studies, several case series, and a plethora of case reports.

 

MEDICAL TREATMENT

 

Therapy for the early stages of HS consists primarily of both topical and systemic antibiotics. Some authors advocate long-term suppressive antimicrobial therapy, although supportive evidence is lacking. Topical clindamycin has been demonstrated to be superior to placebo in a randomized clinical trial. A randomized controlled study comparing topical clindamycin with systemic tetracycline did not reveal a statistical difference.

Intralesional corticosteroids may be of benefit for patients with an isolated number of tender lesions. Practically, such treatment may not be appropriate for individuals with extensive disease and is not appropriate for areas of chronic inflammation.

Isotretinoin as therapy for patients with HS initially held conceptual promise because both diseases share follicular occlusion in disease development. Unfortunately, isotretinoin has demonstrated only a modest therapeutic benefit. In a study of 68 patients, 23.5 percent cleared during therapy, whereas only 16.2 percent maintained improvement during a follow-up period of up to 6 months.¹²⁴ One case report described an individual with severe vulvar HS who, after treatment with prednisolone and then long-term isotretinoin (more than 1 year), remained disease free at 10 months post-treatment. The other systemic retinoids, acitretin and etretinate, have also demonstrated limited efficacy in disease management.

The analogy between acne and HS has also made hormonal therapy for HS appealing. Hormonal therapy does have some reported success. In a double-blinded study, the anti-androgen, cyproterone acetate (50 mg), in conjunction with ethinyl estradiol (50 µg), resulted in complete or partial clearance at 18 months post-treatment in 50 percent of patients. The 5α-reductase inhibitor, finasteride (1 mg), may also have a weak limited effect on disease management.

Infliximab, a chimeric monoclonal antitumor necrosis factor antibody, has demonstrated efficacy in several case reports. Efficacy has been reported in two patients with Crohn disease and HS.^77,129 Infliximab also was efficacious in achieving remission and controlling disease flares in an individual with HS and ulcerative colitis. Case reports or small case series have also shown therapeutic success with other systemic therapies, including systemic corticosteroids, azathioprine, cyclosporine, dapsone, and methotrexate.Local therapies have also been recently examined. A single patient with aggressive perianal HS has responded favorably to wide surgical excision in conjunction with perilesional granulocyte-macrophage colony-stimulating factor injections. A small case series demonstrated the efficacy of treatment of persistent painful nodules with cryotherapy. Healing time in these patients was lengthy (18 to 42 days). Finally, the first case of botulinum toxin A successfully treating HS has been reported. In this case, injections into the axillae resulted in a 10-month remission.

Photodynamic therapy (PDT) as treatment for HS has recently been described in two small case series. In one, four patients sustained 75 percent to 100 percent improvement over 3 months after treatment with aminolevulinic acid-PDT and blue light. In the other case series, three patients receiving aminolevulinic acid-PDT with either a diode

laser (633 nm) or broad band red light source (570 to 670 nm) did not experience clinical improvement.

 

SURGERY

 

Surgical removal of all involved tissue, beyond clinically involved margins, is an effective treatment modality. Postoperative recurrences may occur. Some authors have advocated the use of CO₂ laser for surgical ablation of tissue. The modality of closure has been a topic of debate. Overall, healing by secondary intent is thought to provide the best outcome. Primary closure, grafting, or flaps have been extensively used, but may be associated with poorer results. In one series of 106 patients, there was a 70 percent recurrence rate requiring subsequent operation in the primary closure cohort and no recurrence in the split-thickness graft and flap groups. A more limited surgical approach also plays a role in disease management. Deroofing or marsupializing of recurrent troublesome lesions or sinus tracts may aid with local control. Lancing an inflammatory lesion is of limited benefit and should be discouraged.

 

RADIOTHERAPY

 

Several authors have reported radiotherapy to be successful in the treatment of HS. Given the often young patient population with HS, long-term side effects must be considered